Influence of functional interleukin 10/tumor necrosis factor-alpha polymorphisms on interferon-alpha, IL-10, and regulatory T cell population in patients with systemic lupus erythematosus receiving antimalarial treatment

Abstract

Objective: As interleukin 10 (IL-10)/tumor necrosis factor-alpha (TNF-alpha) polymorphisms have been shown to influence TNF-alpha inhibition and clinical response to antimalarial treatment in patients with systemic lupus erythematosus (SLE), we investigated involvement of these variants in antimalarial effects on cytokine serum levels and regulatory T cell population (Treg).

Methods: The alleles present at -308 TNF-alpha and -1082 IL-10 genes; serum concentrations of interferon-alpha (IFN-alpha), IL-10 and TNF-alpha; and size and function of CD4+CD25(high) (Treg) population were determined in SLE patients and in healthy controls. These data were related to treatment and clinical manifestations.

Results: Patients were observed to have increased IFN-alpha serum levels that did not correlate with any treatment. Among patients receiving antimalarial drugs, high IL-10/low TNF-alpha producers presented higher levels of IFN-alpha and IL-10 than carriers of other genotypes. In contrast, patients with the converse, low IL-10/high TNF-alpha genotype who were receiving antimalarial treatment presented increased size and function of Treg population. The percentage of CD4+CD25(high) cells was inversely correlated to TNF-alpha levels.

Conclusion: Our findings suggest that the beneficial effect of antimalarials in low IL-10/high TNF-alpha patients with SLE may be partially attributable to the increase in Treg activity, whereas patients with the converse genotype did not show this phenomenon, yet did have significantly upregulated levels of IFN-alpha and IL-10, 2 cytokines that have been associated with SLE activity.